ST14 encodes matriptase, a transmembrane serine protease with trypsin-like activity that cleaves substrates with Arg or Lys at the P1 site 1. The primary physiological function of matriptase involves terminal differentiation of keratinocytes through activation of prostasin (PRSS8) and processing of filaggrin (FLG) 2. Additionally, matriptase proteolytically activates the related protease TMPRSS13 3. Mutations in ST14 cause autosomal recessive congenital ichthyosis 11, reflecting its essential role in skin barrier development and keratinocyte differentiation. In cancer biology, matriptase expression levels influence breast cancer prognosis—reduced matriptase protein expression predicts poorer survival, and a specific ST14 variant (rs704624) independently predicts adverse breast cancer outcomes 4. ST14 DNA methylation patterns also correlate with overall survival in breast cancer patients, with high methylation associated with longer survival and higher hormone receptor positivity 5. Matriptase exhibits tumor-suppressive properties through cell cycle regulation, reducing proliferation and invasion in breast cancer cells 6. As a cell surface protein, matriptase is subject to proteolytic cleavage by neutrophil elastase during inflammatory conditions 7.